tbuckley/cabot-search huggingface dataset:
Ethical Restraint Use With Incapable Absconding Patients: Goals, Proportionality, and Surrogates
Authors: Tyler S. Gibb, Kathryn E. Redinger, Hayley Barker
Journal: The American Journal of Bioethics (2022)

This article refers to:“For Your Own Good”? Is It Ethical to Use Chemical Restraints on Patients Who Lack Capacity but Wish to Leave the Hospital against Medical Advice?
PB1794: EFFECT OF HYPOXIA ON CD47 EXPRESSION IN HUMAN ACUTE MYELOID LEUKEMIA CELL LINES
Authors: C. Wang, Y. Liu
Journal: HemaSphere (2022)

Background: To investigate the effect of hypoxia on hypoxia-inducible factor 1α(HIF-1α) and CD47 expression in human acute myeloid leukemia (AML) cell lines. Aims: To investigate the effect of hypoxia on hypoxia-inducible factor 1α(HIF-1α) and CD47 expression in human acute myeloid leukemia (AML) cell lines. Methods: The detection of CD47 expression on U937、HL-60 and K562 cells were evaluated by flow cytometry. U937、HL-60 and K562 cells were all divided into 2 groups, including hypoxia-treated group and conventional oxygen group as control. The U937、HL-60 and K562 cells in hypoxia-treated group were treated with 1%O2, while the cells in control group were cultured in conventional oxygen condition (20%O2), then the cells in 2 groups were collected after treatment for 24 hours. Real time PCR was used to examine the mRNA changes of CD47. Western blot assay was applied to detect the protein expression of HIF-1α and CD47. Results: The expression of CD47 in U937、HL-60 and K562 cells were 98%(98%±0.03), 99%(99%±0.05) and 75%(75%±0.11) respectively. The real time PCR showed that the mRNA expression of CD47 in U937 and HL-60 cells of hypoxia group were upregulated (P<0.05). However, the mRNA expression of CD47 in K562 cell of hypoxia group was not upregulated (P>0.05). The results of Western blot showed that after treatment of U937、HL-60 and K562 cells with hypoxia, the protein levels of HIF-1α and CD47 were increased compared with those in the control group (P<0.05). Summary/Conclusion: The hypoxia can up-regulate the expression of CD47 in acute myeloid leukemia cells, which may be related to HIF-1α.
P1640: SINGLE NUCLEOTIDE POLYMORPHISMS OF THE HIF1A GENE ARE ASSOCIATED WITH SENSITIVITY OF GLUCOCORTICOID TREATMENT IN PEDIATRIC ITP PATIENTS
Authors: H. Gu, X. Xie, J. Ma, L. Fu, J. Ma, R. Wu, Z. Chen
Journal: HemaSphere (2022)

Background: Hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in both innate and adaptive immunity. Emerging evidence indicates that HIF-1α is associated with the inflammation and pathologic activities of autoimmune diseases，suggesting that HIF1α may be involved in immune dysregulation in patients with immune thrombocytopenia (ITP). Aims: The purpose of this study was to evaluate whether single nucleotide polymorphisms (SNPs) of the HIF1A gene are associated with susceptibility to ITP and its clinical prognosis including incidence of chronic immune thrombocytopenia (CITP) and glucocorticoid sensitivity. Methods: This study involved 197 Chinese ITP pediatric patients (discovery cohort) and 220 healthy controls. The Sequenom MassArray system (Sequenom, San Diego, CA) was used to detect three SNPs genotypes in the HIF1A gene: rs11549465, rs1957757 and rs2057482. We also employed another ITP cohort (N = 127) to validate the significant results of SNPs found in the discovery cohort. Results: The frequencies of the three SNPs did not show any significant differences between the ITP and healthy control groups. The CT genotype at rs11549465 was significantly higher in ITP patients sensitive to glucocorticoid-treatment than in those insensitive to glucocorticoid-treatment (P = .025). These results were validated using another ITP cohort (N =127, P = .033). Moreover, the CC genotype was a risk factor for insensitive to GT the OR (95% confidence interval) was 5.96(5.23-6.69) in standard prednisone (PDN) (P=.0069) and 6.35(5.33-7.37) in high-dose dexamethasone (HDD) (P=.04). Summary/Conclusion: Although HIF1A gene polymorphisms were not associated with susceptibility to ITP, the CT genotype at rs11549465 was associated with the sensitivity to glucocorticoid-treatment of ITP patients, suggesting that the rs11549465 SNP may contribute to the sensitivity of glucocorticoid treatment in pediatric ITP patients.
PB1817: PROGNOSTIC SIGNIFICANCE OF CD200 ON ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA AND ITS MECHANISM
Authors: X. Quan, D. Huang, J. Li, T. Yang, Y. Liu
Journal: HemaSphere (2022)

Background: The prognostic significance of CD200 expression in adult AML (non-M3) patients is still unknown. Aims: To analyze the prognostic significance of CD200 expression in newly diagnosed adult patients with non-M3 acute myeloid leukemia (AML) in our department, and to explore the effect of CD200 expression on lymphocyte subsets of patients. Methods: The subject was 86 adult patients with AML (non-M3) who were newly diagnosed from April 2018 to December 2020. Clinical information of these patients was collected, and their survival station was followed up to analyze the connection between CD200 and 1-year overall survival (OS) rate. Patients who received chemotherapy were further evaluated, analyzing the relationship between CD200 expression and other clinical characteristics, as well as the relationship between CD200 and complete response (CR) after the first chemotherapy. And the effect of CD200 expression on lymphocyte subsets of patients was analyzed. Results: Of our study of 86 patients, 60 patients were given chemotherapy. These 60 patients were divided into CD200 + AML and CD200 - AML group according to the CD200 expression. There were no differences between CD200+AML group and CD200-AML group in parameters such as gender, age, white blood cell count and proportion of bone marrow blast cells. The difference of CR rate between two groups was statistically significant (p = 0.025). Univariate and multivariate logistic analysis of potential influencing factors for CR rate showed that CD200 was an independent influencing factor for CR rate after the first course of chemotherapy, and the probability of obtaining CR in the CD200 negative group was 4.15 times that of the CD200 positive group (P =0.018). Among them, 30 patients were stratified to moderate risk according to 2021 NCCN guidelines of AML. The CR rate between CD200 negative and CD200 positive subgroups was compared, and the CR rate in the CD200 negative subgroup was higher than that in the CD200 positive subgroup, but there was no statistical significance (P=0.056). There was no difference in 1-year OS rate between the two groups. Among patients included in the study, there was no significant difference in the percentage of T lymphocytes, regulatory T lymphocytes, NK cells and other subsets in WBC between the CD200+AML group and the CD200-AML group. Summary/Conclusion: In summary, our data suggest that CD200 expression in adult AML (non-M3) patients indicated poor CR rate after the first course of chemotherapy, in the follow-up data of this study so far, CD200 had no prognostic significance for 1-year OS rate. There was a correlation between CD200 expression and CR rate in patients of moderate risk, but there was no statistical significance. Moreover, our data suggest that CD200 expression had no significant effect on lymphocyte subsets in patients.
Smart Compression Therapy Devices for Treatment of Venous Leg Ulcers: A Review
Authors: Gustavo Coelho Rezende, Brendan O'Flynn, Conor O'Mahony
Journal: Advanced Healthcare Materials (2022)

Venous leg ulcers can have significant social and economic impacts, and are generally treated by applying compression to the lower limb, which aids in promoting blood return to the heart. Compression therapies commonly involve the use of passive bandages that suffer from issues associated with incorrect application, and although automated solutions have begun to appear; these are often bulky and hinder mobility. Emerging microtechnologies and new materials enable the development of "smart" compression therapy devices, which are defined as systems that use miniaturized and lightweight actuators and electronics to control the applied pressure. This paper reviews the state of the art in smart compression therapy research. A total of seventeen different devices has been identified, categorized as using one of three actuation mechanisms: pneumatic compression, motor-driven mechanisms, and smart materials (including shape memory alloys, shape memory polymers, and electroactive polymers). The field is still in its relative infancy and further refinements are required to create mass manufacturable compression dressing systems that meet medical, ergonomic, and economic standards. The use of miniaturized actuators has immense potential for the development of smart compression dressings, which will ultimately lead to higher compliance, increased patient comfort, enhanced mobility, and better treatment outcomes.
Highly protective antimalarial antibodies via precision library generation and yeast display screening
Authors: Bailey B. Banach, Prabhanshu Tripathi, Lais Da Silva Pereira, Jason Gorman, Thuy Duong Nguyen, Marlon Dillon, Ahmed S. Fahad, Patience K. Kiyuka, Bharat Madan, Jacy R. Wolfe, Brian Bonilla, Barbara Flynn, Joseph R. Francica, Nicholas K. Hurlburt, Neville K. Kisalu, Tracy Liu, Li Ou, Reda Rawi, Arne Schön, Chen-Hsiang Shen, I-Ting Teng, Baoshan Zhang, Marie Pancera, Azza H. Idris, Robert A. Seder, Peter D. Kwong, Brandon J. DeKosky
Journal: The Journal of Experimental Medicine (2022)

The monoclonal antibody CIS43 targets the Plasmodium falciparum circumsporozoite protein (PfCSP) and prevents malaria infection in humans for up to 9 mo following a single intravenous administration. To enhance the potency and clinical utility of CIS43, we used iterative site-saturation mutagenesis and DNA shuffling to screen precise gene-variant yeast display libraries for improved PfCSP antigen recognition. We identified several mutations that improved recognition, predominately in framework regions, and combined these to produce a panel of antibody variants. The most improved antibody, CIS43_Var10, had three mutations and showed approximately sixfold enhanced protective potency in vivo compared to CIS43. Co-crystal and cryo-electron microscopy structures of CIS43_Var10 with the peptide epitope or with PfCSP, respectively, revealed functional roles for each of these mutations. The unbiased site-directed mutagenesis and screening pipeline described here represent a powerful approach to enhance protective potency and to enable broader clinical use of antimalarial antibodies.
P893: CARFILZOMIB IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE (KRD) AS SALVAGE THERAPY FOR MULTIPLE MYELOMA PATIENTS: ITALIAN, MULTICENTER, RETROSPECTIVE EXPERIENCE OUTSIDE OF CLINICAL TRIALS
Authors: E. A. Martino, C. Conticello, E. Zamagni, V. Pavone, S. Palmieri, M. Musso, P. Tacchetti, A. Mele, L. Catlano, E. Vigna, A. Bruzzese, F. Mendicino, C. Botta, D. Vincelli, G. Farina, M. Barone, C. Cangialosi, K. Mancuso, I. Rizziello, S. Rocchi, A. P. Falcone, G. Mele, G. Reddiconto, B. Garibaldi, E. Iaccino, G. Tripepi, F. Di Raimondo, P. Musto, A. Neri, M. Cavo, F. Morabito, M. Gentile
Journal: HemaSphere (2022)

Background: Carfilzomib in combination with lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. Efficacy and safety of the triplet outside clinical trial are still the object of investigation by many groups to confirm ASPIRE results in the setting of RRMM treated in real-life who don’t meet clinical trial restrictive inclusion criteria. Aims: The aim of the present study is to investigate the efficacy and safety of KRd regimen in the setting of RRMM treated in real-life. Methods: Here we report a retrospective multicenter analysis of 600 RRMM patients treated with KRd between December 2015 and December 2018 Results: The median age at KRd start was 64 years (range 33-85) and the median number of previous therapies was 2 (range 1-11). After a median number of 11 KRd cycles, the ORR was 79.9%. The median PFS was 22 months and the 2-year probability of PFS was 47.6%. At multivariate analysis advanced ISS (III), and high-risk cytogenetic were significantly associated with shorter PFS. The median OS was 34.8 months; the 2-year probability of OS was 63.5% At multivariate analysis creatinine clearance<30 ml/min, more than 1 line of previous therapy, and high-risk FISH were significantly associated with poor prognosis. After a median follow-up of 16 months (range 1-50), 259 withdrew from therapy. The main reason for discontinuation was progressive disease (81.8%). Seventy-four patients (12.3%) discontinued therapy for toxicity. The most frequent side effects were hematological (anemia 49.3%, neutropenia 42.7%, thrombocytopenia 42.5%) and cardiovascular (hypertension 14.5%, heart failure 2.5%, arrhythmias 3.6%). Summary/Conclusion: Our study confirms the safety and efficacy of KRd in the real-life setting of RRMM patients and encourages its use in clinical practice.
P1645: THE SEVERITY OF HEMORRHAGIC SYNDROME AND THE WEAKENING OF THE PROCOAGULANT ACTIVITY OF PLATELETS IN PATIENTS WITH WISKOTT-ALDRICH SYNDROME.
Authors: D. Polokhov, A. Ignatova, E. Ponomarenko, A. Poletaev, P. Zharkov
Journal: HemaSphere (2022)

Background: Patients with Wiskott-Aldrich syndrome (WAS) have a reduced platelet count. Bleeding occurs in most patients and may result in death in 4–10%. The role of impaired procoagulant activity of platelets in WAS has not been studied enough. Aims: To study the role of the weakening of the platelets procoagulant activity in the development of hemorrhagic syndrome. Methods: We examined 25 patients with WAS, observed from June 2017 to January 2020. The median age was 2 years (9 months to 18 years). Patients complained of hemorrhagic manifestations. The severity of hemorrhagic syndrome was assessed using the Pediatric bleeding questionnaire (PBQ). Patients were divided into 2 subgroups depending on the severity of bleeding from 0 to 2 score (n=12) and 3-6 score (n=13). The control group (CG) included 42 healthy children, median age 10 years (from 2-17 years). Flow cytometry was used to determine the total number of platelets and the proportion of phosphatidylserine-positive (PS+) platelets at rest and after activation with a mixture of TRAP-6 and CRP. Statistical differences were analyzed using the Mann-Whitney test with a significance level of p<0.05. Results: The platelet count was lower in patient subgroups compared with CG (p<0.001), but did not differ between patient subgroups (p=1). In the subgroup of patients with bleeding from 0 to 2 points, the proportion of PS+ platelets at rest did not differ from CG (p=0.89), and after activation it was reduced (p<0.001). In the subgroup of patients with bleeding from 3 to 6 points, the proportion of PS+ platelets was lower compared with CG at rest (p=0.02) and after activation (p<0.001). After activation, the proportion of PS+ platelets in CG was ≥ 5%. In 10 (40%) patients, a decrease in platelet PS+ <5% correlated negatively with an increase in the severity of bleeding (corr.= -0.65, p=0.04). Summary/Conclusion: The weakening of the ability to generate procoagulant platelets in patients with Wiskott-Aldrich syndrome was related with an increase in the severity of hemorrhagic syndrome.
PB2276: EARLY ADMINISTRATION OF REMDESIVIR PLUS CONVALESCENT PLASMA THERAPY IS EFFECTIVE TO TREAT COVID-19 PNEUMONIA IN B-CELL DEPLETED PATIENTS WITH HEMATOLOGICAL MALIGNANCIES
Authors: L. I. Pinczes, F. Magyari, E. Páyer, K. Farkas, S. Ujfalusi, Á. Diószegi, A. Deme, M. Sik, G. Nagy, Z. Hevessy, B. Nagy, Á. Illés
Journal: HemaSphere (2022)

Background: Patients with hematological malignancies are at a higher risk of developing severe form and protracted course of COVID-19. Remdesivir, an inhibitor of RNA polymerase was identified early as a promising therapeutic regimen for COVID-19, while convalescent plasma (CP) therapy with anti-SARS-CoV-2 antibodies can aid the treatment of COVID-19 in B-cell depleted patients. Aims: Here we investigated whether the combination of externally administered immunoglobulins (Ig) via CP therapy and specific inhibition of viral replication might be sufficient to effectively treat B-cell depleted patients with COVID-19. Methods: We enrolled a series of 20 consecutive patients who suffered from various hematological malignancies with profound B-cell lymphopenia and COVID-19 pneumonia between December 2020 and May 2021. These patients demonstrated a profound B-cell lymphopenia based on flow cytometry analysis of peripheral blood lymphocyte subpopulations. Consequently, they showed undetectable baseline anti-SARS-CoV-2 Ig levels before CP therapy according to anti-SARS-CoV-2 nucleocapsid- and S1-RBD-specific total Ig tests. Each patient received a complete course of remdesivir and at least one unit (200 ml) of AB0 compatible convalescent plasma during their treatment for COVID-19. Results: Previous anti-CD20 therapy resulted in a more prolonged SARS-CoV-2 PCR positivity compared to other causes of B-cell lymphopenia (p=0.004). Timing of CP therapy showed a significant impact on the clinical outcome. Simultaneous use of remdesivir and CP reduced time period for oxygen weaning after diagnosis (p=0.017), length of hospital stay (p=0.007), and PCR positivity (p=0.012) compared to patients who received remdesivir and CP consecutively. In addition, time from the diagnosis to CP therapy affected the length of oxygen dependency (p<0.001) and hospital stay (p<0.0001). In those cases where there were at least ten days from the diagnosis to plasma administration, oxygen dependency was prolonged vs. patients with shorter interval (p<0.001). Summary/Conclusion: Via combined administration of remdesivir and CP, we experienced an overwhelming survival rate in COVID-19 patients with hematological malignancies. Inhibition of viral replication with passive immunization proved to be efficient and safe. Our results suggest the clear benefit of early administration of CP to avoid protracted COVID-19 disease in patients with B-cell lymphopenia.
PB2107: CLINICAL MANIFESTATIONS AND EFFICACY ANALYSIS OF 71 CASES OF AIDS-RELATED LYMPHOMA
Authors: J. Liu, W. Zhang, T. Yang, Q. Li, J. Li, Y. Xiang, Y. Liu
Journal: HemaSphere (2022)

Background: Patients with AIDS-related lymphoma (ARL) is difficult to accept standard treatment for various reasons. Aims: To summarize the clinical characteristics of AIDS-related lymphoma (ARL) patients admitted to Chongqing Cancer Hospital and improve the understanding of the disease. Methods: The clinical data of 71 ARL patients admitted from January 2008 to January 2021 were retrospectively analyzed. Results: The ratio of male to female in 71 ARL patients was 6.1:1, and the median age was 50 years. Fifty-one percent of patients had no other HIV-related manifestations and were only found at the time of lymphoma diagnosis. 20% of patients were diagnosed with lymphoma within 1 year of AIDS diagnosis and antiviral therapy. At the time of diagnosis of lymphoma, 35 cases (49.3%) with CD4+ cell count>200×10^6/L, 22 cases (30.9%) with CD4+ cell count 100-200×10^6/L, and CD4+ cell count<100×10^6/L and 6 cases of <50×10^6/L (accounting for 8.5 ), and 2 other cases are unknown. The most common pathological type in the 71 patients was diffuse large B-cell lymphoma (38 cases, accounting for 53.5%), Burkitt lymphoma (13 cases, accounting for 18.3), and the types also include Hodgkin lymphoma, high-grade B-cell lymphoma, plasmablastic lymphoma, follicular lymphoma, marginal zone B-cell lymphoma tumor, CLL/SLL, T lymphoblastic lymphoma and Castleman disease. Thirty patients (42.3%) had extranodal involvement at the initial diagnosis, including lung, kidney, intestinal, pancreas, breast, testis, skin and soft tissue involvement. Ann-Arbor staging included 56 patients (78.8%) with stage III-IV, and 19 patients (26.8%) with B symptoms. Survival analysis showed that patients with central involvement, elevated LDH, and intermediate-high-risk IPI scores had shorter progression-free survival, and patients with large masses, intermediate-high-risk and high-risk IPI scores had shorter overall survival. Both CHOP and EPOCH-based chemotherapy regimens are used in AIDS-related non-Hodgkin lymphoma, but the efficacy varies greatly. ABVD treatment of AIDS-related Hodgkin lymphoma is effective, but extranodal involvement may be a poor prognostic factor. Summary/Conclusion: ARL has diverse clinical manifestations, frequent extranodal involvement, late clinical stage, high malignancy, and poor clinical efficacy.
Addressing Racial and Ethnic Differences in Diagnostic Resolution of Abnormal Mammographic Findings
Authors: Randy C. Miles
Journal: JAMA Oncology (2022)

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